Electroactive scaffolds of biodegradable polyurethane/polydopamine-functionalized graphene oxide regulating inflammatory response and revitalizing axonal growth cone for peripheral nerve regeneration

Long-gap peripheral nerve injury remains a major challenge in regenerative medicine and results in permanent sensory and motor dysfunction. Nerve guidance scaffolds (NGSs) are known as a promising alternative to autologous nerve grafting. The latter, the current "gold standard" in clinical practice, is frequently constrained by the limited availability of sources and the inevitable damage to the donor area. Given the electrophysiological properties of nerves, electroactive biomaterials are being intensively investigated in nerve tissue engineering. In this study, we engineered a conductive NGS compounded of biodegradable waterborne polyurethane (WPU) and polydopamine-reduced graphene oxide (pGO) for repairing impaired peripheral nerve. The incorporation of pGO at the optimal concentration (3 wt%) promoted in vitro spreading of Schwann cells (SCs) with high expression of the proliferation marker S100 protein. In an in vivo study of sciatic nerve transection injury, WPU/pGO NGSs were found to regulate the immune microenvironment by activating macrophage M2 polarization and upregulate growth-associated protein 43 (GAP43) to facilitate axonal elongation. Histological and motor function analysis demonstrated that WPU/pGO NGSs had a neuroprosthetic effect close to that of an autograft, which significantly promoted the regeneration of myelinated axons, reduced gastrocnemius atrophy, and enhanced hindlimb motor function. These findings together suggested that electroactive WPU/pGO NGSs may represent a safe and effective strategy to manage large nerve defects.